Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial

医学 彭布罗利珠单抗 易普利姆玛 临床终点 内科学 不利影响 队列 临床试验 实体瘤疗效评价标准 黑色素瘤 胃肠病学 外科 耐火材料(行星科学) 临床研究阶段 免疫疗法 癌症 天体生物学 物理 癌症研究
作者
Caroline Robert,Antoni Ribas,Jedd D. Wolchok,F. Stephen Hodi,Omid Hamid,Richard Kefford,Jeffrey S. Weber,Anthony M. Joshua,Wen-Jen Hwu,Tara C. Gangadhar,Amita Patnaik,Roxana Dronca,Hassane M. Zarour,Richard W. Joseph,Peter D. Boasberg,Bartosz Chmielowski,Christine Mateus,Michael A. Postow,Kevin Gergich,Jeroen Elassaiss‐Schaap
出处
期刊:The Lancet [Elsevier BV]
卷期号:384 (9948): 1109-1117 被引量:1726
标识
DOI:10.1016/s0140-6736(14)60958-2
摘要

The anti-programmed-death-receptor-1 (PD-1) antibody pembrolizumab has shown potent antitumour activity at different doses and schedules in patients with melanoma. We compared the efficacy and safety of pembrolizumab at doses of 2 mg/kg and 10 mg/kg every 3 weeks in patients with ipilimumab-refractory advanced melanoma.In an open-label, international, multicentre expansion cohort of a phase 1 trial, patients (aged ≥18 years) with advanced melanoma whose disease had progressed after at least two ipilimumab doses were randomly assigned with a computer-generated allocation schedule (1:1 final ratio) to intravenous pembrolizumab at 2 mg/kg every 3 weeks or 10 mg/kg every 3 weeks until disease progression, intolerable toxicity, or consent withdrawal. Primary endpoint was overall response rate (ORR) assessed with the Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) by independent central review. Analysis was done on the full-analysis set (all treated patients with measurable disease at baseline). This study is registered with ClinicalTrials.gov, number NCT01295827.173 patients received pembrolizumab 2 mg/kg (n=89) or 10 mg/kg (n=84). Median follow-up duration was 8 months. ORR was 26% at both doses--21 of 81 patients in the 2 mg/kg group and 20 of 76 in the 10 mg/kg group (difference 0%, 95% CI -14 to 13; p=0·96). Treatment was well tolerated, with similar safety profiles in the 2 mg/kg and 10 mg/kg groups and no drug-related deaths. The most common drug-related adverse events of any grade in the 2 mg/kg and 10 mg/kg groups were fatigue (29 [33%] vs 31 [37%]), pruritus (23 [26%] vs 16 [19%]), and rash (16 [18%] vs 15 [18%]). Grade 3 fatigue, reported in five (3%) patients in the 2 mg/kg pembrolizumab group, was the only drug-related grade 3 to 4 adverse event reported in more than one patient.The results suggest that pembrolizumab at a dose of 2 mg/kg or 10 mg/kg every 3 weeks might be an effective treatment in patients for whom there are few effective treatment options.Merck Sharp and Dohme.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
易燃物品完成签到,获得积分10
刚刚
Hello应助Ther采纳,获得10
2秒前
CherylZhao完成签到,获得积分10
3秒前
Galato发布了新的文献求助10
4秒前
颜愫完成签到,获得积分10
4秒前
安详向日葵完成签到 ,获得积分10
5秒前
拼搏的白云完成签到,获得积分10
5秒前
852应助hhh采纳,获得10
5秒前
李白白白完成签到,获得积分10
5秒前
王手完成签到,获得积分10
5秒前
6秒前
一人完成签到,获得积分10
7秒前
do0完成签到,获得积分10
8秒前
yar应助xlz110采纳,获得10
8秒前
NexusExplorer应助落寞凌波采纳,获得10
10秒前
量子星尘发布了新的文献求助10
13秒前
123完成签到 ,获得积分10
13秒前
哈哈呵完成签到,获得积分10
13秒前
13秒前
Rylee完成签到,获得积分10
13秒前
Jiro完成签到,获得积分10
15秒前
我ppp发布了新的文献求助60
16秒前
17秒前
纳米酶催化完成签到,获得积分10
18秒前
18秒前
John完成签到,获得积分10
18秒前
李小强完成签到,获得积分10
19秒前
20秒前
23秒前
落寞凌波发布了新的文献求助10
23秒前
23秒前
24秒前
健壮的尔烟完成签到,获得积分10
24秒前
三三完成签到 ,获得积分10
24秒前
白betty完成签到,获得积分10
26秒前
双儿发布了新的文献求助10
27秒前
好吃完成签到,获得积分10
28秒前
duoduo完成签到 ,获得积分10
29秒前
29秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038368
求助须知:如何正确求助?哪些是违规求助? 3576068
关于积分的说明 11374313
捐赠科研通 3305780
什么是DOI,文献DOI怎么找? 1819322
邀请新用户注册赠送积分活动 892672
科研通“疑难数据库(出版商)”最低求助积分说明 815029